US11834475B2ActiveUtilityA1

Alphavirus nsP mutants as vaccines

60
Assignee: AGENCY SCIENCE TECH & RESPriority: Feb 7, 2017Filed: Aug 19, 2021Granted: Dec 5, 2023
Est. expiryFeb 7, 2037(~10.5 yrs left)· nominal 20-yr term from priority
Inventors:Lisa Fong Poh NgYi Hao ChanAndres MeritsAge Utt
C07K 14/005A61K 9/127A61K 39/12A61P 31/14A61K 2039/5254A61K 2039/5258A61K 2039/54A61K 2039/542A61K 2039/543A61K 2039/545C12N 2770/36122C12N 2770/36123C12N 2770/36134C12N 2770/36171Y02A50/30
60
PatentIndex Score
0
Cited by
17
References
34
Claims

Abstract

Provided herein are polypeptides, polynucleotides, expression vectors, infectious clones, virus particles and immunogenic compositions of recombinant alphaviruses which can be used as vaccines. Also provided are methods for eliciting an immune response against alphavirus infection using the immunogenic composition comprising the alphavirus mutants described herein.

Claims

exact text as granted — not AI-modified
The invention claimed is: 
     
       1. A polynucleotide encoding a recombinant alphavirus non-structural protein (nsP) polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 1 or a variant thereof comprising at least 80% identity to the amino acid sequence set forth in SEQ ID NO: 1, wherein said polypeptide or said variant thereof comprises an amino acid mutation at a position equivalent to amino acid position R532 of SEQ ID NO: 1, and/or an amino acid mutation at a position equivalent to amino acid position E1050 of SEQ ID NO: 1. 
     
     
       2. A polynucleotide encoding a recombinant alphavirus non-structural protein (nsP) polypeptide comprising an amino acid mutation at a position equivalent to amino acid position R532 of SEQ ID NO: 1, and/or an amino acid mutation at a position equivalent to amino acid position E1050 of SEQ ID NO: 1. 
     
     
       3. The polynucleotide of  claim 1 , wherein the recombinant polypeptide comprises the amino acid sequence set forth in SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. 
     
     
       4. The polynucleotide of  claim 1 , wherein the mutation comprises a missense mutation and/or an amino acid substitution. 
     
     
       5. The polynucleotide of  claim 1 , wherein the mutation at position 532 comprises a substitution of R with H. 
     
     
       6. The polynucleotide of  claim 1 , wherein the mutation at position 1050 comprises a substitution of E with V. 
     
     
       7. The polynucleotide of  claim 1 , wherein the polynucleotide is DNA or RNA. 
     
     
       8. The polynucleotide of  claim 1 , wherein the polynucleotide comprises the nucleotide sequence set forth in SEQ ID NO: 5, SEQ ID NO:6, SEQ ID NO: 7, or a variant thereof comprising at least 80% nucleotide sequence identity to SEQ ID NO: 5, SEQ ID NO: 6, or SEQ ID NO: 7, wherein the nucleotide sequence encodes a polypeptide comprising an amino acid mutation at a position equivalent to amino acid position R532 of SEQ ID NO: 1, and/or an amino acid mutation at a position equivalent to amino acid position E1050 of SEQ ID NO: 1. 
     
     
       9. The polynucleotide of  claim 1 , wherein the recombinant polypeptide comprises at least 85% identity to the amino acid sequence set forth in SEQ ID NO: 1. 
     
     
       10. The polynucleotide of  claim 1 , wherein the recombinant polypeptide comprises at least 90% identity to the amino acid sequence set forth in SEQ ID NO: 1. 
     
     
       11. The polynucleotide of  claim 1 , wherein the recombinant polypeptide comprises at least 95% identity to the amino acid sequence set forth in SEQ ID NO: 1. 
     
     
       12. The polynucleotide of  claim 1 , wherein the recombinant polypeptide comprises the amino acid sequence set forth in SEQ ID NO: 1. 
     
     
       13. The polynucleotide of  claim 1 , wherein the polynucleotide comprises at least 85% nucleotide sequence identity to SEQ ID NO: 5, SEQ ID NO: 6, or SEQ ID NO: 7. 
     
     
       14. The polynucleotide of  claim 1 , wherein the polynucleotide comprises at least 90% nucleotide sequence identity to SEQ ID NO: 5, SEQ ID NO: 6, or SEQ ID NO: 7. 
     
     
       15. The polynucleotide of  claim 1 , wherein the polynucleotide comprises at least 95% nucleotide sequence identity to SEQ ID NO: 5, SEQ ID NO: 6, or SEQ ID NO: 7. 
     
     
       16. The polynucleotide of  claim 1 , wherein the polynucleotide comprises the nucleotide sequence set forth in SEQ ID NO: 5, SEQ ID NO: 6, or SEQ ID NO: 7. 
     
     
       17. A vector comprising the polynucleotide of  claim 1 . 
     
     
       18. A recombinant virus particle comprising a polypeptide encoded by the polynucleotide of  claim 1 . 
     
     
       19. The polynucleotide of  claim 2 , wherein the recombinant polypeptide comprises the amino acid sequence set forth in SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. 
     
     
       20. The polynucleotide of  claim 2 , wherein the mutation comprises a missense mutation and/or an amino acid substitution. 
     
     
       21. The polynucleotide of  claim 2 , wherein the mutation at position 532 comprises a substitution of R with H. 
     
     
       22. The polynucleotide of  claim 2 , wherein the mutation at position 1050 comprises a substitution of E with V. 
     
     
       23. The polynucleotide of  claim 2 , wherein the polynucleotide is DNA or RNA. 
     
     
       24. The polynucleotide of  claim 2 , wherein the polynucleotide comprises the nucleotide sequence set forth in SEQ ID NO: 5, SEQ ID NO:6, SEQ ID NO: 7, or a variant thereof comprising at least 80% nucleotide sequence identity to SEQ ID NO: 5, SEQ ID NO: 6, or SEQ ID NO: 7, wherein the nucleotide sequence encodes a polypeptide comprising an amino acid mutation at a position equivalent to amino acid position R532 of SEQ ID NO: 1, and/or an amino acid mutation at a position equivalent to amino acid position E1050 of SEQ ID NO: 1. 
     
     
       25. The polynucleotide of  claim 2 , wherein the recombinant polypeptide comprises at least 85% identity to the amino acid sequence set forth in SEQ ID NO: 1. 
     
     
       26. The polynucleotide of  claim 2 , wherein the recombinant polypeptide comprises at least 90% identity to the amino acid sequence set forth in SEQ ID NO: 1. 
     
     
       27. The polynucleotide of  claim 2 , wherein the recombinant polypeptide comprises at least 95% identity to the amino acid sequence set forth in SEQ ID NO: 1. 
     
     
       28. The polynucleotide of  claim 2 , wherein the recombinant polypeptide comprises the amino acid sequence set forth in SEQ ID NO: 1. 
     
     
       29. The polynucleotide of  claim 2 , wherein the polynucleotide comprises at least 85% nucleotide sequence identity to SEQ ID NO: 5, SEQ ID NO: 6, or SEQ ID NO: 7. 
     
     
       30. The polynucleotide of  claim 2 , wherein the polynucleotide comprises at least 90% nucleotide sequence identity to SEQ ID NO: 5, SEQ ID NO: 6, or SEQ ID NO: 7. 
     
     
       31. The polynucleotide of  claim 2 , wherein the polynucleotide comprises at least 95% nucleotide sequence identity to SEQ ID NO: 5, SEQ ID NO: 6, or SEQ ID NO: 7. 
     
     
       32. The polynucleotide of  claim 2 , wherein the polynucleotide comprises the nucleotide sequence set forth in SEQ ID NO: 5, SEQ ID NO: 6, or SEQ ID NO: 7. 
     
     
       33. A vector comprising the polynucleotide of  claim 2 . 
     
     
       34. A recombinant virus particle comprising a polypeptide encoded by the polynucleotide of  claim 2 .

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